Micropump

ABSTRACT

This invention provides a fluid pump using perforate elements and closure elements which are alternately displace and relates particularly but not exclusively to miniature fluid pumps and pumps suitable for delivery of liquid pharmaceutical formulations. In the art of miniature liquid pumps are known pumps based on peristaltic and “pump chamber” principles. (Peristaltic pumps may be used to pump fluids in general, that is, liquids or gases). Both types of pump are used in ambulatory pump products for delivery of liquid medicaments, for which application miniaturization and low weight are important attributes.

[0001] The present invention provides a new type of fluid pumpapparatus, and one that is particularly suitable for (but not limitedto) application in miniature ambulatory liquid drug pumps.

[0002] Although not essential in some applications, it is oftendesirable that the fluid pump (‘pump’ for short) does not allow‘back-flow’; that is, it does not allow fluid flow in the direction fromthe pump outlet to the pump inlet. Back-flow can be caused by arelatively high hydrostatic head at the outlet compared to the inlet.This is particularly important in the case of drug pumps, whereback-flow can result in fluid loss or sterility issues for the drugreservoir. It is also often desirable that the pump does not allowuncontrolled “forward flow”. In the case of drug pumps, uncontrolledforward flow can result in overdosing to the patient.

[0003] Fluid naturally flows from a region at which its hydrostaticpressure is high to a region where its hydrostatic pressure is low. Thisdirection of flow is not always desirable; for example, in medicine itis often desirable to introduce liquid drugs into the venous or arterialsystem of patients, as a means of administering therapy. To improvetheir quality of life, it is often desirable to do so when they are freeto walk, rather than to be confined to a bed. In such a situation, thedrug reservoir is often, for practical purposes, desirably attached tothe patient's body, and consequently is generally at a hydrostaticpressure that is lower than the patient's venal or arterial pressure.The pump must therefore deliver a volume of fluid (in this case, aliquid drug formulation) from a region of low pressure (the reservoir)at the inlet side of the pump to a region of higher pressure (thepatient's bloodstream) at the outlet side of the pump. To do so, thepump must be capable of creating a rise in pressure of the fluid to bepumped and to displace a volume of fluid at that increased pressure,i.e. the pump must be capable of doing hydrostatic work on the fluid.Furthermore, the pump should not allow uncontrolled forward flow either.

[0004] This is quite general and so, for the purposes of thisspecification, we define a fluid pump (whether an ambulatory drug pumpor other type of pump) to be an apparatus that is capable of doing workupon a fluid by transporting a volume of that fluid from a first region(the pump inlet) to a second region (the pump outlet). If the mechanismcannot do this, it does no work on the fluid and so, failing in itsfundamental function, it is not a fluid pump.

[0005] In the art of peristaltic drug pumps, drug formulation is fedfrom a reservoir to an outlet (which is typically terminated by a needleinserted into a patient) via a length of tubing. In use, a solid bodycompresses the tubing locally and, whilst maintaining that localcompression, the solid body moves along the tubing in the direction fromthe reservoir to the outlet. The motion of this compressing bodydisplaces fluid against the higher fluid pressure on the outlet side,thereby doing work on the fluid as it does so. This process is repeated,most typically by employing a sequence of such solid bodies in the formof cylindrical rollers mounted off the axis of a rotating shaft tosequentially squeeze and translate along the tube. Each solid bodyreleases from the tube only when the immediately following solid bodyestablishes tube compression on the inlet side of the tube relative tothe releasing solid body. In this way, a pumping action is establishedthat does not permit significant ‘back-flow’. Since the pipe is alwaysclosed, uncontrolled forward flow is not permitted.

[0006] Such pumps are well known, but it has proven difficult tominiaturize them to the level desired by many patients using ambulatorypumps. They occasionally have problems of imperfect sealing of the tube(so some back-flow can occur) and fatigue of the tube can occur due tothe repeated tube compression; further, the act of compressivetranslation is energetically lossy and requires significant powerconsumption, so limiting minimum pump size. Finally, such pumps producea noticeable and undesirable low-frequency ‘pulsatile’ flow as the solidbodies move into and out of tube compression.

[0007] CH-C-280618 by Sigg describes a pump provided with a chamberhaving an inlet, an outlet and, disposed between the inlet and theoutlet, a plate member which is movable in a reciprocal motion withinthe chamber. The plate member is provided with a number of nozzles whichare shaped so as to offer greater resistance to the flow of a fluid fromthe outlet side to the inlet side of the plate member than to the flowof fluid from the inlet side to the outlet side of the plate member. Inthis way, as the plate member is moved in a reciprocating motion in thechamber, the net flow of fluid is from the inlet to the outlet side ofthe pump. Whilst this pump creates a net flow to the outlet, it requiresfurther apparatus to prevent unwanted ‘back flow’ in the case when thereis a greater pressure at the outlet than at the inlet or to preventuncontrolled forward flow when there is a greater pressure at the inletthan at the outlet.

[0008] In the art of ‘pump chamber’ pumps, there is provided a pumpchamber or volume that may be varied by an actuator and having one-wayvalves at both inlet and outlet, both valves being arranged to allowflow in the direction from the inlet to the outlet. The inlet valve islocated between the pump chamber and the reservoir and the outlet valveis located between the pump chamber and the delivery site. In use, thetubing between at least the inlet valve (and usually from reservoir todelivery site) and the outlet valve is filled with liquid, and the pumpchamber volume is alternately increased (to ingest further liquidthrough the inlet valve whilst the outlet valve is closed) and reduced(to expel that ingested volume of liquid through the outlet valve whilstthe inlet valve is closed) by the action of the actuator. The one-wayvalve therefore acts to rectify the flow. The actuator may be asolenoid, a piezoelectric actuator or other type of electromechanicalactuator. The pump is resistant to “back flow” by the arrangement of thevalve mechanisms, however additional components are required to preventuncontrolled forward flow.

[0009] A more recent variant of such pumps is described by Stemme, seefor example, WO-A-94/19609. In this device, there is provided a pumpchamber, in use filled with liquid, in which the inlet and outletone-way valves of conventional ‘pump chamber’ pumps are replaced byfluid flow constrictions. These flow constrictions have, for a givenflow through them, a larger pressure drop in one flow direction (whichhe terms the ‘nozzle direction’) than in the opposite flow direction(which he terms the ‘diffuser direction’). So Stemme replacesconventional ‘one-way’ valves that have a better flow rectificationaction with valves that have no requirement for mechanical motion andare therefore more robust than the standard displacement pumps.

[0010] This pump therefore requires auxiliary means to preventundesirable ‘back-flow’ and forward flow when an opposing hydrostaticpressure head (that is, a pressure difference against which the pump inuse does hydrostatic work) is present. From the description, furtherauxiliary means appear desirable to suppress the pulsatile nature of theliquid flow, so it appears that the pump operates at low cyclefrequencies.

[0011] In both the Stemme pump and the ‘pump chamber’ pumps havingconventional one-way valves (‘conventionally valved’), effective pumpingis based upon the incompressibility of the liquid and the mechanicalstiffness of the pump chamber. Both require components providing partialor complete flow rectification (valve action) at both the inlet and theoutlet (whether those components are conventional one-way valves or the‘flow restrictors’ of Stemme). They need components providing valveaction at the inlet in order that such liquid incompressibility results,on decrease of the pump chamber volume, in expulsion of liquid throughthe outlet. They need components providing valve action at the outlet inorder that such liquid incompressibility results, on increase of thepump chamber volume, in ingestion of liquid through the inlet valve.Both forms have a relatively complex three-dimensional form, which isrelatively expensive to produce.

[0012] The reliance of these pumps upon mechanically stiff pump chambersand the near-incompressibility of the liquid being pumped means that,for example, if air or other gas is present in the pump chamber, some orall of the volume reduction on the ‘ejection’ stroke is used up incompressing the (easily-compressible gas) before expelling liquidthrough the outlet and some or all of the volume increase on the‘ingestion’ stroke is used up in rarefying the (easily-rarefied) gasbefore ingesting liquid through the inlet. Consequently a reduced, orzero, quantum of liquid is actually pumped per cycle of operation andpumping capability is reduced or lost. Further, since the bubbleexpansion is not, in general, equal to the bubble compression (due to aprocess known from the ink jet printing art as ‘rectified diffusion’),this also creates increasing errors in the fluid volume delivered percycle. These failings are particularly serious in the case of liquiddrug delivery, especially those drugs that are kept in a cool (oftenrefrigerated) state until the time of use in order to extend theiruseful shelf life. On pump delivery of such drugs to the patient, thedrug is exposed to higher ambient temperatures, the solubility of anyair dissolved in the drug liquid decreases, and some of the dissolvedair often comes out of solution in the form of air bubbles. This effectmakes accurate delivery of such drugs very difficult by such ‘pumpchamber’ pumps. As can be appreciated, ‘pump chamber’ pumps are not, tothe knowledge of the present inventors, able to pump liquid and gasmixtures effectively.

[0013] One aspect of fluid pump devices, which significantly increasetheir usefulness for liquid delivery, is their ability to self-prime.When the inlet pipe is placed within a body of liquid to be pumped, avolume of air is trapped between the liquid meniscus in the inlet pipeand the outlet. Self-priming occurs when this air is displaced throughthe pump from the inlet to the outlet by the action of the pumpmechanism, thereby drawing the liquid at the inlet through the pump tothe outlet.

[0014] It is recognised by the applicant that “fluid” has a dual meaningof both a gas, such as air, and a liquid. Also recognised is that afluid pump is able to pump both gas and liquid, and further that a fluidpump is capable of self-priming.

[0015] There are also known in the art apparatus and methods foratomising liquids into droplets, in which the liquid is brought to oneface of a membrane having orifices, which membrane is then vibrated athigh frequency. One such apparatus is described in patent applicationEP-A-0 655 256 to provide the transport of bulk liquid from one face tothe opposing face of such a membrane before such atomisation occurs. Inthis art however, the liquid is transported from a region of higherhydrostatic pressure to a region of lower hydrostatic pressure. The roleof the vibration appears to assist the natural liquid flow (in thedirection encouraged by the hydrostatic pressure difference) through theorifices by overcoming the opposition of the menisci that are initiallypresent at those orifices. There is no teaching in that application ofmeans to prevent ‘back-flow’ that otherwise would occur when such anopposing hydrostatic pressure is present.

[0016] A simple vibrating pump is described by Maehara in JP-A-58-140491in which a pressurising chamber has, as an outlet, a nozzle platethrough which a number of nozzles have been bored. The nozzle plate iscaused to vibrate by a piezoelectric oscillator such that the fluid inthe chamber is ejected through the nozzle plate as a spray. There is noteaching of any means for preventing ‘backflow’.

[0017] EP-1099853 discloses a diaphragm breakage protection system in areciprocating diaphragm pump. The pump is provided with a chamber inwhich a moveable diaphragm is mounted. An exit location from the chamberis covered with a moveable plate, in which a series of perforations areprovided. The perforated plate covers the exit point from the chamberand prevents the diaphragm, when in its deflected state, passing intothe outlet. When in the at rest position, the diaphragm and theperforate element are spaced apart, thus allowing either forward orbackward flow through the perforate element. Furthermore, as the pumpincludes a sealed chamber, the operation of the pump is then intolerantto the presence of air within the chamber, such that the performance ofthe pump would be quickly depreciated should air enter the chamber.

[0018] The present invention seeks to overcome at least some of theaforementioned disadvantages of the known peristaltic fluid or liquidpumps and the ‘pump chamber’ liquid pump and the liquid ‘atomiser’device and to provide a smaller or simpler pump than hitherto has beenprovided.

[0019] According to a first aspect of the present invention, there isprovided a method of pumping a fluid, the method comprising:

[0020] supplying a fluid to at least one side of a perforate element,the perforate element having one or more perforations and beingadjacent, on the one side, to at least one closure assembly whichprevents fluid flow through the one or more perforations when the pumpis not in use; and

[0021] providing a net transfer of fluid through the perforate elementin the direction from the one side to the other side of the perforateelement by alternately displacing the perforate element in directionstowards and away from the one side and by alternately displacing the atleast one closure element in directions towards and away from the oneside.

[0022] According to a second aspect of the present invention, there isprovided a pump for pumping a fluid, the pump comprising:

[0023] an inlet;

[0024] an outlet;

[0025] a perforate element disposed between the inlet and the outlet,the perforate element having one or more perforations;

[0026] at least one closure assembly disposed adjacent said perforateelement on the one side and having at least one closure aligned with atleast one of the perforations in the perforate element to close saidperforation(s) when the pump is not in use, and

[0027] a drive means for alternately displacing the perforate element indirections towards the inlet and outlet sides of the pump.

[0028] Thus, the present invention provides a method of pumping and apump which prevents unwanted forward flow and back flow when not in useand which, as no sealed chamber is required, ensures that the pump istolerant to the presence of air or gas bubbles within the liquid to bepumped.

[0029] When the displacements are in phase, fluid is permitted to flowthrough the perforation(s) as the closure assembly moves away from theperforate element at the peak in the cycle of the perforate element. Thedifference between the vibration amplitudes of the perforate element andthe closure assembly is the valve open gap.

[0030] When the displacements are out of phase, the valve open gap isthe sum of the vibration amplitudes of the perforate element and theclosure assembly. In this arrangement, the perforation(s) is (are) openwhen the membrane is moving away from the closure assembly and closedwhen the membrane is deflected towards the closure assembly.

[0031] Preferably the closure assembly is displaced out of phase withrespect to the perforate element.

[0032] In this regard, out of phase motion is defined as when the phaseangle between the motion of the closure assembly and of the perforateelement is non-zero. Another definition of out of phase relative motionwhich also applies is when the perforate element is moving periodicallytowards and away from the closure assembly. It is important to note thatsuch motion does not necessarily require touching contact between theclosure assembly and the perforate element on each cycle, as may occurfor non-periodic motion of the closure assembly for example. The motionin the out of phase mode is most regular when the phase angle is 180°,and touching contact is achieved between the closure assembly and theperforate element on each cycle.

[0033] It is preferable for the displacements of the perforate elementand/or the closure assembly to be resonant.

[0034] Preferably, the inlet is the one side of the perforate element atwhich the fluid has the lower hydrostatic pressure and the outlet is theother side of the perforate element at which the fluid has the higherhydrostatic pressure.

[0035] Preferentially, the perforate element takes the form of a thinmembrane or plate with perforations therethrough (such as may befabricated for example by electroforming, laser machining or dischargemachining operations). Alternatively, the perforations could be formedby simple mechanical drilling.

[0036] The closure assembly may take the form of a spring and valvemass. The spring may be a cantilever beam or may comprise a centralplate portion for contacting the valve mass and having a plurality oflegs extending between the plate portion and the perforate element.

[0037] The drive means may take the form of an electromechanicalactuator and an electronic drive circuit that, in use, is mechanicallycoupled to the perforate element. Preferentially the drive means iscapable of generating high accelerations of the perforate element butwith small physical displacements, as will be explained further by wayof the example below. Further, the drive means preferentially displacesthe perforate element in such a manner that following one completemotion (that is a motion substantially in the direction towards and awayfrom the inlet), the perforate element is restored to its initialposition. For these purposes piezoelectric, piezomagnetic orelectrostrictive actuators are highly desirable; their rapid responsecharacteristics allow high accelerations, whilst their physicaldisplacements are very small.

[0038] The perforate element, the electromechanical actuator of thedrive means and the closure assembly taken together are hereinafterreferred to as the ‘pump head’. By integrating the electromechanicalactuator, particularly where it is of piezoelectric or electrostrictivetype, with the perforate element a ‘solid state’ pump head of very smallsize and low power consumption and operating to pump fluid with verysmall motional displacements can be provided.

[0039] Preferably, the fluid is pumped from a first region (the pumpinlet) at which it is at a relatively low hydrostatic (as distinct fromhydrodynamic) pressure to a second region (the pump outlet) at which itis at a relatively high hydrostatic pressure. Fluid may be loaded toeither the inlet side of the pump or to both sides of the pump.

[0040] The invention will now be described with reference to thefollowing drawings, in which:

[0041]FIG. 1 shows a pump according to the present invention;

[0042]FIG. 2 shows detail of a pump head according to the presentinvention, within the pump;

[0043]FIG. 3 shows a schematic representation of one arrangement of theperforate element and the closure assembly of the present invention;

[0044]FIGS. 4a and 4 b show a schematic representation of the pumping ina first mode;

[0045]FIGS. 5a and 5 b show a schematic representation of pumping in asecond mode;

[0046]FIG. 6 is a graph indicating mode frequency as a function ofquarter wavelength of the valve spring indicated in FIG. 3;

[0047]FIG. 7 shows the construction of one form of a closure assembly;

[0048]FIG. 8 shows a three dimensional image, taken with a PolytecScanning Vibrometer PSV 300 (Polytec GmbH, Walbronn, Germany), showingthe perforate element and the closure assembly in the first mode(maximum displacement);

[0049]FIGS. 9a and 9 b show the vibration amplitude and phaserelationship in the first mode;

[0050]FIG. 10 is a three dimensional image taken with a Polytec ScanningVibrometer PSV 300 (Polytec GmbH, Walbronn, Germany) the perforateelement and closure assembly in the second mode maximum displacement;

[0051]FIGS. 11a and 11 b are representative of the vibration amplitudeand phase relationship in the second mode;

[0052]FIG. 12 is a graph indicating the performance of a resonant valve;

[0053]FIGS. 13a and 13 b show another schematic representation of theperforate element and closure assembly; and

[0054]FIGS. 14a, 14 b and 14 c are schematic plan views of other formsof spring.

[0055] In FIG. 1 is shown a pump 20 comprising: a pump head 1 having aninlet 5 and an outlet 6, an electrical drive circuit 21 and a powersupply 22 to which pump head 1 is electrically connected by means ofwires 11. By way of example only, a fluid reservoir 24 is connected tothat pump by means of inlet tubing 14, and an outlet 23, in the form ofa syringe needle, is connected to that pump by means of outlet tubing15. In use, these are typically arranged so that the hydrostaticpressure of fluid at inlet 5 is lower than the hydrostatic pressurepresented at outlet 6 although this does not have to be the case. (Mosttypically the pressure in reservoir 24, for example in ambulatory drugpumps, will be lower than that at the outlet needle 23.)

[0056]FIG. 2 shows detail of one form of pump head 1, without theclosure assembly 13 shown in FIGS. 3,4,5,7,8 and 10, together withancillary components of an overall pump system. Pump head 1, which hasoverall cylindrical symmetry, is mounted on a mounting body 2. Itcomprises an electromechanical actuator 3 mechanically coupled to aperforate element 4 having perforations in region 7. Perforate element 4has opposing inlet 5 and outlet 6. Region 7 of perforate element 4 istypically formed as a stainless steel membrane or plate of thicknesstypically in the region of 20 μm to 200 μm and diameter typically 1 mmto 5 mm. Through the thickness of region 7, perforations, whose minimumsize is typically in the range 3 μm to 100 μm, are formed by laserdrilling. Alternative membrane or plate materials include electroformednickel; in that case the perforations may be introduced as a result ofthe electrochemical growth process of the membrane, rather than laterintroduced. When using electroformed nickel for drug deliveryapplications, it is generally desirable to coat the nickel andperforations with a layer of a relatively inert material such as gold orpara-xylylene (‘parylene’) so that nickel does not become extracted intothe drug formulation being pumped. That layer must be applied thinlyenough that it does not block the perforations. Alternatively, thematerial may be formed from a stainless steel, or other suitable metal,through which the perforation(s) are mechanically drilled. In this case,the perforations are typically in the range 100 μm to 500 μm. Theremaining portion of perforate element 4 may be formed, for example, ofstainless steel; its dimensions (except where specified) are notcritical but preferably are chosen such that the total mass of body 4 isof similar magnitude to, or less than, that of the actuator 3.

[0057] Actuator 3 is an electromechanical actuator in the form of acylindrical tube of piezoelectric ceramic material mounted on mountingbody 2. Actuator 3 has electrodes 9 and 10 on the inner and outercylindrical surfaces. Electrode 10 ‘wraps around’ one end of the tubefor easier electrical connection, but unlike electrode 9 it does notsubstantially extend across the outer cylindrical surface of theactuator. It is connected by wires 11 to an electrical drive circuit(not shown). Actuator 3 is conveniently a piezoelectric ceramic ofmaterial grade PIC151 from Lambda Physik of Germany (or some similargrade from other suppliers) and is 4 mm in outside diameter, 2.5 mm ininternal diameter, and 12 mm long.

[0058] In use, the fluid 8 to be pumped is brought at relatively lowhydrostatic pressure to inlet 5. As described with reference to FIG. 1,this is typically, though not necessarily, by means of an inlet tube 28.Similarly, typically though not necessarily, fluid at relatively highpressure is transported away from outlet 6 by means of outlet tube 29.

[0059] Drive circuit 21 provides electrical excitation of actuator 3 tocause lengthways contractional and extensional displacements of an endsurface 12 of actuator 3, and, in consequence, perforate region 7 ofperforate element 4 is displaced alternately between directions towardsand away from inlet 5. These alternating motions occur rapidly. Inresonant motion, the typical frequency for the dimensions of actuator 3given above is (when the excitation is continuous and resonant ratherthan intermittent) approximately 100 kHz, but the precise frequency ofoperation depends upon the precise geometry of the actuator 3 anddetails of the mounting of actuator 3 to mounting body 2. Intermittentoperation is also possible, in which case it is more sensible to thinkof ‘rise times’ of the displacement motion rather than operatingfrequency; in this case ‘rise times’ are typically in the μs regime. Thedisplacements of perforate element 4 are usually small, typically lessthan 1 μm. However the high frequency (or short ‘rise time’) combinewith those displacements to produce high accelerations, typically in therange 10 ⁴ m/s²-10⁶ m/s². The higher values of acceleration are mostconveniently achieved in a continuously oscillating system in which themechanical system of actuator 3 and perforate element 4 is mechanicallyin resonance.

[0060]FIG. 3 shows a schematic representation of the centre of perforateelement 4 and includes, at least in part, region 7 in which theperforations are formed. The perforate element 4 is provided with asingle nozzle 14 which, in this example, is provided with parallel sidessuch that the cross sectional area of each side of the nozzle 14 is thesame. A closure assembly 13, taking the form of a cantilever spring, islocated such that a closure, in this case a substantially spherical mass15, is adjacent one side of the nozzle 14. The closure assembly ismounted to an external solid fixing point 19 (see FIG. 7) and is setwith a sufficient pre-load force to seal the nozzle against forwards andbackwards flow.

[0061] The interaction between these reciprocating displacements ofperforate region 7, the closure assembly 13 and the fluid 8 can thenproduce a pumping action in one of two ways, according to the detailedmode of excitation of the perforate element and the closure assembly, asfurther described with reference to FIGS. 4a, 4 b, 5 a and 5 b below.Description of operation is made in the case where the inlet side of theperforate element is at relatively low hydrostatic pressure and theoutlet side at relatively high hydrostatic pressure.

[0062]FIGS. 4a and 4 b show a schematic representation of the pumpingaction in the first mode in which the motion of the perforate element 4and the closure member 13 is resonant and in phase. Whilst it ispreferable for the motion to be resonant, it is not essential. In thisarrangement, on each cycle, the membrane 4 drives the valve mass 15attached to the closure assembly 13 up and down, at resonance and inphase with the motion of the membrane. In an alternative arrangement notshown by the figures, the closure assembly may be driven not by themembrane but a separate driving means. In FIG. 4a, the valve is openedas the valve mass 15 moves away from the nozzle 14 and, in FIG. 4b, thevalve is shown closed as the closure assembly 13 moves towards thenozzle 14. It should be noted that the valve open gap is the differencebetween the vibration amplitudes of the valve mass 15 and the membrane4. In this arrangement, the fluid is pumped in the direction shown byarrow 16 from the open side of the nozzle to the side on which theclosure assembly is located. Thus, the region of lower hydrostaticpressure should be located on the open side of the nozzle 14 (the lowerside as shown in FIGS. 4a and 4 b).

[0063] In the arrangement shown in FIGS. 5a and 5 b, on each cycle, themembrane drives the valve mass 15 up and down at resonance and out ofphase with the membrane motion. As with the first mode, in analternative arrangement not shown by the figures, the closure assemblymay be driven not by the membrane but a separate driving means. Againresonant motion is preferred but is not essential. In this way, thevalve open and valve close positions of the cycle is reversed whencompared to the arrangement shown in FIGS. 4a and 4 b so that the nozzle14 is closed when the membrane 4 is deflected towards the valve mass 15,and open when the membrane 4 is moving away from the valve mass 15. Inthis arrangement, the valve open gap is the sum of the vibrationamplitudes of the membrane 4 and the valve mass 15 in the out of phasemotion, the fluid is caused to flow in the direction shown by arrow 17,that is from the side of the nozzle on which the closure assembly 13 islocated to the open side of the nozzle. In this case, the region oflower hydrostatic pressure should be on the same side of the nozzle asthe closure assembly 13. The profile of the nozzle 4 can be any suitableshape. However, it is preferable for the cross-section to be circularand for the valve mass 15 to be spherical.

[0064] Whilst only a single closure assembly having a single valve masshas been described in these examples, it is envisaged that pluralclosure assembly may be used and that each closure assembly may havemore than one valve mass.

[0065] The following dispersion relation has been used to specify thevalve spring:

ω=k ² Eh ²/(12ρ(1−σ²))

[0066] where ω is the resonant frequency of the nozzle valve, k=2πT/λ,and E is the Young's modulus of the valve spring, h is the thickness ofthe valve spring, ρ is the density of the valve spring and σ is thePoisson's ratio for the valve spring. The geometry of the valve springis such that the length of the valve spring is controlled to define thewavelength of the valve spring vibration.

[0067] For resonant motion of the closure assembly with the membrane,the closure assembly 13 may be characterised by the solution to aresonant beam model in which the quarter wavelength (or, in fact, anywavelength having the form λ(1/4+n/2) where n is zero or any positiveinteger) of the vibration is matched to the length of the beam and thestiffness is matched to a chosen mode frequency of the nozzle plate 4.

[0068] For a stainless steel beam, where the Young's modulus (E) is 2.010¹¹N/M², this relationship may be used to generate the frequenciesshown in FIG. 6, where mode frequency is expressed as a function ofquarter wavelength and beam thickness.

[0069] The applicants have created devices which have operated atapproximately 70 kHz, using 100 μm thick beams and, in this arrangement,the quarter wavelength of such a vibration is approximately 2.4 mm.Thus, to optimise the resonance of this valve spring at 70 kHz, thelength of the valve tip 18 shown in FIG. 7 could be 2.4 mm (n=O), 7.2 mm(n=1), 12.0 mm (n=2), etc from its mounted position. The closureassembly 13 can be seen mounted in a rigid spring mount 19.

[0070] The resonant modes of operation were investigated by theapplicants with a laser vibrometer using simple laboratory apparatus toreport the valve structure.

[0071]FIG. 8 is a representation showing the three dimensional image ofthe perforate membrane 4 with the closure assembly 13 highlighted as asegment, intercepting the centre of the membrane to cover the singlenozzle 14. By studying the locus of points defined in the cross-sectionA-A, it can be seen from this Figure that the displacement amplitude ofthe membrane 4 and the closure assembly 30 is between 600 nm and 900 nmover the nozzle region, thus indicating a nozzle opening of no more than300 nm.

[0072] From section A-A, it is also possible to determine the nozzleopening and this is indicated in FIG. 9a. This shows the peak amplitudeand vibration across the diameter of the membrane 4, intercepting theclosure element 13 at the centre. From this Figure, it can be seen thatthe nozzle opening aperture us very small, typically no more than 100nm. By analysing the same section across the membrane for phaseinformation, the applicants have obtained the graph shown in FIG. 9b.This indicates that the membrane and the valve are both vibrating inphase with each other, and thus 90° out of phase with the AC drivesignal. Therefore this valve is operating in the first resonant mode.

[0073]FIG. 10 shows a similar representation to that of FIG. 8 but inwhich the membrane 4 was oscillated at a frequency of 86 kHz. In thismode, the length of the valve tip 18 is 7.0 mm. At 86 kHz, the 100 μmthick valve spring has a quarter wavelength of 2.3 mm and therefore thevalve tip correlates to 0.76 λ (n=1). From FIG. 10, it can be seen thatthe closure assembly 13 is vibrating with much greater amplitude ofvibration (in excess of 1 μm) relative to the membrane. By analysing thesection B-B across the diameter of the membrane the applicants haveobtained the information shown in FIGS. 11a and 11 b. FIG. 11a showsthat the opening aperture of the nozzle valve is at least 500 nm. InFIG. 11b, it can be seen clearly that the closure assembly is vibratingat approximately 180° out of phase with the membrane. According to thissecond mode of vibration this is resonant, out of phase operation. Inthis second mode, it has been found that, when operated to pump,approximately 0.7 micro litre per second can be pumped against a backpressure of 500 mbar (the pressure difference between the outlet and theinlet). It was also shown to deliver forward pump flow at a backpressure up to 600 mbar and this can be seen from FIG. 12 which is agraph indicating the performance of an out of phase resonant valve inwhich the nozzle diameter is 250 μm and the fluid being pumped issaline.

[0074] In another arrangement of a perforate element and a closureassembly shown in FIG. 13a, a perforate element 30 is mounted on oneside of a stainless steel substrate 31, the perforate element 30 havinga perforation 32 therethrough. A spring 33 extends over the perforation32 in such a way that it retains a closure member 34, in this case asapphire sphere, so that the sphere rests in and seals around the edgeof perforation 32. On the other side of the stainless steel substrate 31to the perforate element 30, a piezoceramic annulus 35 is attached. Byapplying an alternating electrical signal between electrodes on theupper and lower faces of the piezoelement 35, the substrate 31 is causedto vibrate thereby causing the valve mass 34 to be moved alternativelytowards and away from the perforation 32. The spring 33, shown ingreater detail in FIGS. 14a, 14 b and 14 c, comprises a central plateportion 41 to which a series of legs 42 are attached. The legs areconnected to an annular portion 43 which is attached to the perforateelement 30. The valve mass 34 is held in compression between the centralplate 41 and the perforate element 30. The mass is spherical and so isfree to rotate, while always ensuring that the circular perforation 32is fully sealed. The mass 34 is centered on the centre of theperforation, since the hub portion 31 does not apply any specificlateral constraint. This improves the tolerance of the manufacturingprocess, since the perforation 32 and valve mass 34 are self aligning.

[0075] In this arrangement, pumping is believed to operate when thevalve mass 34 and the perforate element 30 vibrate in out of phasemotion. This is particularly true when the valve mass 34 is stationaryand the perforate element 30 is moving towards and away from it.

[0076] In FIG. 13b, the piezo element 35 and perforate element 30 haveswapped sides of the stainless steel substrate, but in each of FIGS. 13aand 13 b, pumping occurs from the side of the perforate element to whichthe mass 34 is positioned towards the other side.

[0077] The provision of valve mass 34 sealing perforation 32 when atrest ensures that unwanted forward flow through the perforate element isprevented and unwanted back flow, in this example upwardly through theperforate element 30, is prevented, up to a certain limit defined by thespring pre-load force provided by spring 33, when it is deflected atrest by approximately the diameter of the valve mass 34.

[0078]FIGS. 14a, 14 b and 14 c show three different types of spring 33,but each of these has a central plate portion 41 and a plurality of legs42 extending from this plate to an annular portion 43, which, in use, isattached to the perforate element 30.

[0079] The invention has been described without reference to fluid flowsensing. Without flow sensing, flow rate of the pump as described aboveis affected by the magnitude of the hydrostatic head against which thepump is delivering fluid (see FIG. 12 for example), so that flow rate isnot precisely known. However, known flow sensing means such as biaspressure measurement, thermal pulse injection or nephelometric or otherforms of optical-scattering sensing means may be used in combinationwith the invention as described above. The output of such sensors may beused to measure actual flow rate and to control and/or maintain adesired flow rate within the range of hydrostatic pressures againstwhich a particular embodiment of the pump itself can deliver fluid. Inthis way accurate fluid volume (or dose) delivery can be provided.

1. A method of pumping a fluid, the method comprising: supplying a fluidto at least one side of a perforate element, the perforate elementhaving one or more perforations and being adjacent, on the one side, toat least one closure assembly which prevents fluid flow through the oneor more perforations when the pump is not in use; and providing a nettransfer of fluid through the perforate element in the direction fromthe one side to the other side of the perforate element by alternatelydisplacing the perforate element in directions towards and away from theone side and by alternately displacing the at least one closure elementin directions towards and away from the one side.
 2. A method accordingto claim 1, wherein the closure assembly is displaced out of phase withthe perforate element.
 3. A method according to either claim 1 or claim2, wherein the displacements are resonant.
 4. A method according to anyone of the preceding claims, wherein the perforate membrane drives thedisplacement of the closure assembly.
 5. A method according to any oneof the preceding claims, wherein the fluid is pumped from a region oflower hydrostatic pressure to a region of higher hydrostatic pressure.6. A pump for pumping a fluid, the pump comprising an inlet; an outlet;a perforate element disposed between the inlet and the outlet, theperforate element having one or more perforations; at least one closureassembly disposed adjacent said perforate element on the one side andhaving at least one closure aligned with at least one of theperforations in the perforate element to close said perforation(s) whenthe pump is not in use, and a drive means for alternately displacing theperforate element in directions towards the inlet and outlet sides ofthe pump.
 7. A pump according to claim 6, wherein the closure assemblyis displaced out of phase with the perforate element.
 8. A pumpaccording to either claim 6 or claim 7, wherein the displacements areresonant.
 9. A pump according to any one of claims 6 to 8, wherein theinlet is the one side of the perforate element at which the fluid hasthe lower hydrostatic pressure and the outlet is the other side of theperforate element at which the fluid has the higher hydrostaticpressure.
 10. A pump according to any of claims 6 to 9, wherein theperforate element takes the form of a thin, stiff membrane or plate withperforations passing therethrough from the inlet to outlet.
 11. A pumpaccording to any one of claims 6 to 10, wherein the drive means takesthe form of an electronic drive circuit and an electromechanicalactuator that, in use, is mechanically coupled to the perforate element.12. A pump according to any one of claims 6 to 11, wherein the drivemeans takes the form of an electronic drive circuit and piezoelectricmaterial in the perforate element.
 13. A pump according to any one ofclaims 6 to 12, wherein the closure assembly comprises a spring and oneor more a valve masses attached to the spring for closing theperforation(s).
 14. A pump according to claim 13, wherein the springincludes a central plate portion for contacting the valve mass andhaving a plurality of legs extending between the plate portion and theperforate element.
 15. A pump according to any one of claims 6 to 14,further comprising drive means attached to the closure assembly.